Disorder of lysine and hydroxylysine metabolism
-Rare genetic disease
Comment:
AASS (alpha-aminoadipate delta-semialdehyde synthase) is a bifunctional enzyme. The reaction forms saccharopine as an intermediate and 2-aminoadipic semialdehyde as the final product. Familial hyperlysinemia includes two conditions: hyperlysinemia type I, which presents with pipecolic aciduria, and hyperlysinemia type II, which presents with saccharopinuria. Defects in one or both activities result in familial hyperlysinemia (PMID:23890588).
Hyperlysinemia is described as a disorder that results from reduced activity of LKR and/or of SDH (PMID:10775527).
Carson et al. (1968) reported saccharopinuria in a 22-year-old moderately retarded, somewhat short girl with EEG abnormalities but no history of seizures; her urine also contained lysine, citrulline, and histidine. No other family members were affected.
... Carson et al. (1968) reported saccharopinuria in a 22-year-old moderately retarded, somewhat short girl with EEG abnormalities but no history of seizures; her urine also contained lysine, citrulline, and histidine. No other family members were affected. Simell et al. (1972) described a 3.5-year-old girl with spastic diplegia who had lysinuria and saccharopinuria, but normal plasma levels of citrulline. Somatically and mentally she was normal. Simell et al. (1973) demonstrated deficiency of the saccharopine-degrading enzyme aminoadipic semialdehyde-glutamate reductase in cultured fibroblasts and in muscle. The enzyme was reduced to 40% of normal. Hyperlysinemia (238700), a similar disease, is due to mutation at a single locus, that coding for the bifunctional enzyme aminoadipic semialdehyde synthase (AASS; 605113) (Sacksteder et al., 2000; Cox and Dancis, 1995). This molecule has both lysine ketoglutarate reductase (LKR) and saccharopine dehydrogenase (SDH) activity, these being the first 2 steps in lysine degradation. (In bacteria, the 2 enzymes are separate.) In hyperlysinemia, both enzyme functions of AASS are defective; in saccharopinemia, some of the first enzymatic function is retained (Cox, 1985; Cox et al., 1985).